Specific Aims: To measure regional brain indices of capillary morphometry such as, diameter, length, surface area, volume and number per cubic mm in various brain regions comparing the total vs. perfused capillary networks in young vs. senescent animals. It has not been possible to selectively examine the perfused capillary bed prior to the development of this new method. Rationale: Cerebral oxygen consumption, the product of blood flow and oxygen extraction, and cerebral blood flow, remain normal in normal healthy elderly patients. Therefore, oxygen extraction must be maintained in spite of a thickening in vessel walls and a decrease in the number of fine capillary networks. It is hypothesized that regional brain oxygen extraction is maintained by changing the percentage of perfused capillaries in the brain, and/or their capillary diameter, surface area, volume, number or length cubic mm perfused capillary morphometry has never been examined during aging. Methodology: These parameters of brain capillary morphometry will be examined regionally according to standard stereological techniques. The perfused capillary bed will be visualized through the systemic injection of a fluorescent dye in pentobarbital anesthetized rats, and subsequent photographing of 2 Mum thick brain slices from 10 brain regions. The sections then will be stained with alkaline phosphatase to visualize the total capillary bed, and rephotographed. These photographs will be matched, compared and analyzed to determine these indices of capillary morphometry regionally in the total vs. perfused brains of young vs. senescent rats. Long-term Objectives: These pilot data using an innovative method, applied to a priority area of research would contribute significantly to an understanding of deficiencies in the control of the cerebral microcirculation during aging which could be correlated with a predisposition toward metabolic or functional disturbances in the elderly. Funding would allow a young investigator to obtain pilot data which would be used to obtain future grant funding which would determine if various drugs or clinical interventions can improve oxygen delivery in senescent humans.